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Pathology, Research and Practice Feb 2023GRP78 is a chaperone with anti-apoptotic function associated with aggressive tumors. This systematic review aimed to evaluate GRP78 expression in cancer and its relation... (Meta-Analysis)
Meta-Analysis Review
GRP78 is a chaperone with anti-apoptotic function associated with aggressive tumors. This systematic review aimed to evaluate GRP78 expression in cancer and its relation to prognosis outcomes. This review was conducted in different databases searching for human cancer studies assessing GRP78 immunohistochemical levels on tissue samples. A total of 98 manuscripts were included. In 62% of the studies, GRP78 was associated with a worse prognosis. A meta-analysis included 29 studies that detected a significantly higher expression of GRP78 in cancer tissues (RR= 2.35, 95% CI 1.75-3.15) compared to control. A meta-analysis of 3 and 5-years Overall Survival revealed an increased risk of death for tumors with high expression of GRP78 (RR=1.36, 95%CI 1.16-1,59, I = 57%) and (RR=1.65, 95%CI 1.22-2.21, I =64%), respectively. GRP78 is an important prognostic biomarker for different types of cancer and a promising therapeutic target.
Topics: Humans; Endoplasmic Reticulum Chaperone BiP; Heat-Shock Proteins; Prognosis; Neoplasms; Biomarkers; Glucose
PubMed: 36610326
DOI: 10.1016/j.prp.2023.154301 -
Current Oncology (Toronto, Ont.) Nov 2022The endoplasmic reticulum chaperone BiP (also known as GRP-78 or HSPA5) maintains protein folding to allow cell proliferation and survival and has been implicated in... (Meta-Analysis)
Meta-Analysis
The endoplasmic reticulum chaperone BiP (also known as GRP-78 or HSPA5) maintains protein folding to allow cell proliferation and survival and has been implicated in carcinogenesis, tumor progression, and therapy resistance. BiP's association with clinical factors and prognostic potential in breast cancer remains unclear. In this work, three types of analysis were conducted to improve the knowledge of BiP's clinicopathological potential: (1) analysis of publicly available RNA-seq and proteomics datasets stratified as high and low quartiles; (2) a systematic review and meta-analysis of immunohistochemical detection of BIP; (3) confirmation of findings by BiP immunohistochemical detection in two luminal-like breast cancer small cohorts of paired samples (pre- vs. post-endocrine therapy, and primary pre- vs. metastasis post-endocrine therapy). The TCGA PanCancer dataset and CPTAC showed groups with high BiP mRNA and protein associated with HER2, basal-like subtypes, and higher immune scores. The meta-analysis of BiP immunohistochemistry disclosed an association between higher BiP positivity and reduced relapse-free survival. BiP immunohistochemistry confirmed increased BiP expression in metastasis, an association of BiP positivity with HER2 expression, and nuclear BiP localization with higher a tumor stage and poor outcome. Therefore, three independent approaches showed that BiP protein is associated with worse outcomes and holds prognostic potential for breast cancer.
Topics: Humans; Female; Endoplasmic Reticulum Chaperone BiP; Heat-Shock Proteins; Breast Neoplasms; Neoplasm Recurrence, Local; Prognosis
PubMed: 36547124
DOI: 10.3390/curroncol29120710 -
Biomolecules Oct 2022Alzheimer's disease (AD) is considered a chronic and debilitating neurological illness that is increasingly impacting older-age populations. Some proteins, including... (Review)
Review
Alzheimer's disease (AD) is considered a chronic and debilitating neurological illness that is increasingly impacting older-age populations. Some proteins, including clusterin ( or ) transporter, can be linked to AD, causing oxidative stress. Therefore, its activity can affect various functions involving complement system inactivation, lipid transport, chaperone activity, neuronal transmission, and cellular survival pathways. This transporter is known to bind to the amyloid beta (Aβ) peptide, which is the major pathogenic factor of AD. On the other hand, this transporter is also active at the blood-brain barrier (BBB), a barrier that prevents harmful substances from entering and exiting the brain. Therefore, in this review, we discuss and emphasize the role of the transporter and -linked molecular mechanisms at the BBB interface in the pathogenesis of AD.
Topics: Humans; Clusterin; Alzheimer Disease; Amyloid beta-Peptides; Blood-Brain Barrier; Membrane Transport Proteins; Lipids
PubMed: 36291661
DOI: 10.3390/biom12101452 -
Medicine Jul 2022The SET-CAN/NUP214 fusion gene resulting from chromosomal del(9)(q34.11q34.13) or t(9;9) (q34;q34) has been found in T-cell acute lymphoblastic leukemia (T-ALL), B-cell...
BACKGROUND
The SET-CAN/NUP214 fusion gene resulting from chromosomal del(9)(q34.11q34.13) or t(9;9) (q34;q34) has been found in T-cell acute lymphoblastic leukemia (T-ALL), B-cell acute lymphoblastic leukemia (B-ALL), acute myeloid leukemia (AML) and myeloid sarcoma (MS). Furthermore, the SET-CAN/NUP214 fusion gene has been found in the T-ALL cell line LOUCY and the AML line MEGAL. The common features of these cases are insensitivity to chemotherapy and poor prognosis. We reviewed the characteristics and prognostic significance of the SET-CAN/NUP214 fusion gene in hematological malignancies.
METHODS
This systematic literature search was conducted using the PubMed, Web of Science, Embase, and Cochrane Library databases. With the inclusion and exclusion criteria, we summarized all of the papers and performed a statistical analyses.
RESULTS
In general, the SET-CAN/NUP214 fusion gene is very rare in adult acute leukemia, more frequently found in T-ALL than in other types of leukemia, and more often in males. Flow cytometry data indicated that the markers CD34, CD33, CD13, and CD7 were common in SET-CAN/NUP214 positive acute leukemia, including ALL. Fluorescence in situ hybridization and arrays are important methods for detecting the fusion gene in newly diagnosed patients and can detect chromosomal del(9)(q34) will be detected. The chromosomal karyotype may be normal or complex, and, in terms of survival analysis, transplantation results in a better prognosis than chemotherapy alone.
CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS
The presence of SET-CAN/NUP214 fusion gene may be a Minimal Residual Disease of early recurrence, and it might be a poor indicator of outcome.
LIMITATIONS
The mechanism, clinical characteristics, therapy and prognosis of the SET-CAN/NUP214 fusion gene in hematological malignancies require further research.
Topics: Adult; DNA-Binding Proteins; Hematologic Neoplasms; Histone Chaperones; Humans; In Situ Hybridization, Fluorescence; Leukemia, Myeloid, Acute; Male; Nuclear Pore Complex Proteins; Oncogene Proteins, Fusion; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Prognosis; Transcription Factors
PubMed: 35905214
DOI: 10.1097/MD.0000000000029294 -
The Science of the Total Environment Sep 2022The effect of high-altitude (HA) on venous thromboembolism (VTE) and its mechanism remains ambiguous. To clarify this, we aimed to conduct a meta-analysis and systematic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The effect of high-altitude (HA) on venous thromboembolism (VTE) and its mechanism remains ambiguous. To clarify this, we aimed to conduct a meta-analysis and systematic review to evaluate the incidence of VTE at HA and comparatively low altitude (LA) and figure out the intrinsic risk factors such as susceptibility genes of patients with VTE at HA.
METHODS
We selected studies that explored the risk factors for HA and VTE by searching PubMed, Embase, and Web of Science to analyze the impact of HA on VTE. All relevant studies before August 2021 were screened using the terms ([high altitude] OR [plateau] OR [mountain]) AND ([venous thromboembolism] OR [deep vein thrombosis] OR [pulmonary embolism]). Latest studies on the gene of HA-VTE patients were also summarized and analyzed.
RESULTS
Fifteen studies were eventually assessed, and the overall numbers of subjects with and without VTE were 1475 and 286,926 respectively. The overall incidence of VTE, deep vein thrombosis (DVT) and pulmonary embolism (PE) in the HA group was significantly higher than that in the LA group (P < 0.01). The overall incidence of VTE, DVT and PE in the HA group was significantly higher than that in the LA group at 30 days post operation (P < 0.05, P < 0.05 and P < 0.01, respectively). At 90 days post operation, incidence of VTE and PE in the HA group was higher than that in the LA group (P < 0.01and P < 0.01, respectively), but there was no difference in the incidence of DVT (P = 0.07). Regarding endogenous factors, the analysis of genes in patients with HA-VTE revealed numerous targeted genes such as ANG, ACE, lncRNA-LINC00 659/UXT-AS1 and GP4.
CONCLUSIONS
We observed a significant association between HA and the overall incidence of VTE and that at 30/90 days post operation, indicating that HA may be a risk factor for VTE.
Topics: Humans; Altitude; Cell Cycle Proteins; Genetic Predisposition to Disease; Incidence; Molecular Chaperones; Pulmonary Embolism; Risk Factors; Venous Thromboembolism; Venous Thrombosis
PubMed: 35691358
DOI: 10.1016/j.scitotenv.2022.156632 -
Cancer Control : Journal of the Moffitt... 2022The previous reports on clusterin (CLU) levels in various types of cancer have been controversial and heterogeneous. The present meta-analysis has aimed to evaluate the... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
The previous reports on clusterin (CLU) levels in various types of cancer have been controversial and heterogeneous. The present meta-analysis has aimed to evaluate the association between soluble CLU levels and the risk of different human cancers based on observational studies.
METHODS
A systematic literature review was conducted to determine the relevant eligible studies in English language from health-related electronic databases up to January 2021. Random effects models were used to calculate the summary standard mean difference (SMD) with 95% confidence intervals (CIs) to identify the correlation between CLU levels and cancer risk. The meta-regression, sensitivity, Galbraith, and subgroup analyses were performed to explore the source of between-study heterogeneity. Furthermore, the funnel plot and Egger's linear regression tests were carried out to evaluate the risk of publication bias.
RESULTS
According to 16 eligible articles, 3331 patients and 839 healthy controls were included in our meta-analysis. Overall, the CLU levels were significantly higher in various cancer cases compared to the healthy groups (SMD = 1.50, 95% CI = 0.47-2.53). Moreover, subgroup analysis based on types of cancer showed a significant correlation between CLU levels and the risk of digestive system cancers (SMD = 1.54, 95% CI = 0.91-2.18, <0.001), especially in HCC (SMD = 1.89, 95% CI = 0.76-3.03, = 0.001), and CRC (SMD = 1.63, 95% CI = 0.0-3.23, = 0.048).
CONCLUSION
The present meta-analysis indicates a significant association of CLU levels with the risk of digestive system cancers such as hepatocellular carcinoma and colorectal cancer. Therefore, CLU can be monitored as a novel molecular biomarker for the prognosis and diagnosis of various types of cancers particularly in the digestive system.
Topics: Carcinoma, Hepatocellular; Clusterin; Humans; Liver Neoplasms; Prognosis; Risk
PubMed: 35465749
DOI: 10.1177/10732748211038437 -
BMC Gastroenterology Nov 2021Heat shock protein 70 (HSP70) has been associated with the clinicopathological characteristics and prognosis of many cancers types, implying that it is a potential... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Heat shock protein 70 (HSP70) has been associated with the clinicopathological characteristics and prognosis of many cancers types, implying that it is a potential cancer biomarker. However, no consensus has been reached regarding its clinicopathological and prognostic significance in patients with gastric cancer. To address this gap, we performed a systematic review and meta-analysis.
METHODS
We searched PubMed, Embase, and the Cochrane Library for full-text literature according to the eligibility criteria. We used the odds ratio and hazard ratio as the suitable parameters to evaluate the clinicopathological and prognostic significance of HSP70. The statistical analysis was performed using STATA 15.0.
RESULTS
After inclusion and exclusion of studies based on the eligibility criteria, data of 1,307 patients with gastric cancer from 9 studies were finally included. The pooled outcomes implied that HSP70 expression was significantly correlated with higher differentiation degrees, intestinal gastric cancer, and lymphovascular invasion but not with age, gender, depth of invasion, Helicobacter pylori infection, lymph node invasion, TNM stages, and metastasis. The pooled HR showed no significant correlation between HSP70 expression and overall survival of gastric cancer patients.
CONCLUSIONS
Our meta-analysis showed that HSP70 plays a complicated role in the development of gastric cancer. It may be directly engaged in tumour differentiation and distant invasion but cannot be considered a biomarker for predicting the prognosis of gastric cancer.
Topics: Biomarkers, Tumor; HSP70 Heat-Shock Proteins; Helicobacter Infections; Helicobacter pylori; Humans; Prognosis; Stomach Neoplasms
PubMed: 34809574
DOI: 10.1186/s12876-021-01990-4 -
Current Problems in Cardiology Feb 2023Transient receptor potential (TRP) family play critical roles in cardiovascular system. TRPM family as largest TRP subfamily is non-voltage Ca2+-activated selective... (Review)
Review
Transient receptor potential (TRP) family play critical roles in cardiovascular system. TRPM family as largest TRP subfamily is non-voltage Ca2+-activated selective channels which has 8 members. This study aimed to discuss the role of TRPM family in cardiovascular system and diseases. Systematic search was performed covering PubMed, ISI Web of Science, and Google Scholar from inception until June 2021 using related keywords and Mesh terms for English studies with human, animal and in-vitro subjects. Finally 10 studies were selected for data extraction. Reviewing the articles showed that TRPM2, TRPM4, TRPM5, TRPM6 and TRPM7 play important roles in cardiovascular system and diseases. TRPM2 could be activated by reactive oxygen species (ROS) and effects on cardiac injury and cardiac fibrosis. TRPM7 and TRPM6 also have been reported to be associated with cardiac fibrosis and atrial fibrosis development respectively. TRPM4 channels contributed to resting membrane potential of cerebral artery smooth muscle cells and atrial contraction. TRPM5 channels are bitter taste sensors and prevent high salt intake and consequently high blood pressure due to the high salt intake. In conclusion based on the proof of the effectiveness of some members of TRPM family in the cardiovascular system, research on other members of this channel group seems to be useful and necessary to find their possible connection to the cardiovascular system.
Topics: Animals; Humans; TRPM Cation Channels; Sodium Chloride, Dietary; Membrane Potentials; Clusterin; Cardiovascular System; Protein Serine-Threonine Kinases
PubMed: 34644560
DOI: 10.1016/j.cpcardiol.2021.101012 -
Biomolecules Jul 2021Alzheimer's disease (AD), a progressive neurodegenerative disease, affects approximately 50 million people worldwide, which warrants the search for reliable new... (Meta-Analysis)
Meta-Analysis
Alzheimer's disease (AD), a progressive neurodegenerative disease, affects approximately 50 million people worldwide, which warrants the search for reliable new biomarkers for early diagnosis of AD. Brain-derived exosomal (BDE) proteins, which are extracellular nanovesicles released by all cell lineages of the central nervous system, have been focused as biomarkers for diagnosis, screening, prognosis prediction, and monitoring in AD. This review focused on the possibility of BDE proteins as AD biomarkers. The articles published prior to 26 January 2021 were searched in PubMed, EMBASE, Web of Science, and Cochrane Library to identify all relevant studies that reported exosome biomarkers in blood samples of patients with AD. From 342 articles, 20 studies were selected for analysis. We conducted a meta-analysis of six BDE proteins and found that levels of amyloid-β42 (standardized mean difference (SMD) = 1.534, 95% confidence interval [CI]: 0.595-2.474), total-tau (SMD = 1.224, 95% CI: 0.534-1.915), tau phosphorylated at threonine 181 (SMD = 4.038, 95% CI: 2.312-5.764), and tau phosphorylated at serine 396 (SMD = 2.511, 95% CI: 0.795-4.227) were significantly different in patients with AD compared to those in control. Whereas, those of p-tyrosine-insulin receptor substrate-1 and heat shock protein 70 did not show significant differences. This review suggested that Aβ42, t-tau, p-T181-tau, and p-S396-tau could be effective in diagnosing AD as blood biomarkers, despite the limitation in the meta-analysis based on the availability of data. Therefore, certain BDE proteins could be used as effective biomarkers for AD.
Topics: Alzheimer Disease; Amyloid beta-Peptides; Biomarkers; Brain; Exosomes; HSP70 Heat-Shock Proteins; Humans; Insulin Receptor Substrate Proteins; Peptide Fragments; tau Proteins
PubMed: 34356604
DOI: 10.3390/biom11070980 -
Frontiers in Endocrinology 2021Pancreatic neuroendocrine tumors (PanNETs) are a heterogeneous group of neoplasms with increasing incidence and unpredictable behavior. Whole-exome sequencing recently... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pancreatic neuroendocrine tumors (PanNETs) are a heterogeneous group of neoplasms with increasing incidence and unpredictable behavior. Whole-exome sequencing recently has shown very frequent somatic mutations in the alpha-thalassemia/mental retardation X-linked (ATRX) and death domain-associated protein (DAXX) genes in PanNETs. And the prognostic significance of altered ATRX/DAXX genes in PanNETs patients have been revealed in several reports. However, many of these include small sample size and hold controversial opinions. To increase statistical power, we performed a systematic review and meta-analysis to determine a pooled conclusion. We examined the impact of altered ATRX/DAXX genes mainly on overall survival (OS), disease-free survival (DFS) and relapse-free survival (RFS) in PanNETs.
METHODS
Eligible studies were identified and quality was assessed using multiple search strategies (last search May 2021). Data were collected from studies about prognostic significance of altered ATRX/DAXX in PanNETs. Studies were pooled, and combined hazard ratios (HRs) with 95% confidence intervals (CIs) were used to estimate strength of the associations.
RESULTS
Fourteen studies involving 2313 patients treated for PanNETs were included. After evaluating for publication bias, disease-free survival and relapse-free survival was significantly shortened in patients with altered ATRX/DAXX gene, with combined HR 5.05 (95% confidence interval (CI): 1.58-16.20, = 0.01) and 3.21 (95% confidence interval (CI): 1.44-7.16, < 0.01) respectively. However, the combined data showed there were no difference between patients with altered ATRX/DAXX gene or not in overall survival, with a combined HR 0.71 (95% confidence interval (CI): 0.44-1.15, = 0.23). We also performed a subgroup analysis with metastatic patients in overall survival, showing a combined HR 0.22 (95% confidence interval (CI): 0.11-0.48, = 0.96). The small number of studies and paucity of multivariate analyses are the limitations of our study.
CONCLUSIONS
This is the first rigorous pooled analysis assessing ATRX/DAXX mutation as prognostic biomarkers in PanNETs. Patients with altered ATRX/DAXX gene would have poor DFS according to the combined data. And altered ATRX/DAXX genes in metastatic patients showed a trend towards improved overall survival, although the difference did not reach statistical significance.
Topics: Co-Repressor Proteins; Humans; Molecular Chaperones; Neuroendocrine Tumors; Pancreatic Neoplasms; Prognosis; X-linked Nuclear Protein
PubMed: 34220718
DOI: 10.3389/fendo.2021.691557